Zinc uptake into fibroblasts is inhibited by probenecid.
Cellular zinc transport has not been fully characterized. The role of an anion carrier was investigated by treating normal human fibroblasts, and those carrying a mutation which affects zinc transport, acrodermatitis enteropathica (AE), with the anion carrier inhibitor, probenecid. Zinc uptake (2, 10, or 20 micromol 1(-1) 65zinc) was determined during initial rates of uptake (15 min) following treatment with 0, 10 or 20 mmol 1(-1) probenecid. Probenecid stimulated extracellular zinc binding in normal and AE fibroblasts. Probenecid inhibited the internalization of zinc in normal, but not AE, fibroblasts. Normal fibroblasts exhibited an apparent Km which was reduced by 53% and 44% in the 10 and 20 mmol 1(-1) probenecid treated cells. The Vmax was also reduced in the normal fibroblasts by 51% and 50% in the 10 and 20 mmol 1(-1) probenecid treated cells. The results suggest that a probenecid-sensitive anion carrier is involved in the internalization of zinc in human fibroblasts. The lack of an effect of probenecid on the internalization of zinc in the AE fibroblasts suggests that the mutation involves a probenecid-sensitive anion transport system, and that there may be a secondary mechanism for zinc transport in these cells.
Chang
C Y
CY
Department of Human Ecology, University of Texas at Austin, 78712, USA.
Muga
S J
SJ
Grider
A
A
D000169:Acrodermatitis / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004705:Endocytosis / Q000187:drug effects; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007223:Infant; D008297:Male; D009154:Mutation; D011339:Probenecid / Q000494:pharmacology*; D015032:Zinc / Q000378:metabolism*
D015032:Zinc; D011339:Probenecid